D-pantolactone has heretofore been prepared through optical resolution of chemically synthesized D,L-pantolactone.
Such process, however, requires the use of costly resolving agents such as quinine or brucine, and suffers from the drawback that the recovery of D-pantolactone is not easy.
Processes of optical resolution of D,L-pantolactone by enzymatic asymmetric hydrolysis have also been known from Japanese published unexamined patent application No. 57-52895 (JP, A, 57-152895) and Japanese published unexamined patent application No. 62-294092 (JP, A, 62-294092). In these processes, the L-pantolactone in D,L-pantolactone is selectively subjected to asymmetric hydrolysis using microorganisms to afford D-pantolactone. These processes have the disadvantage that L-pantolactone, not being completely hydrolysable, does not yield D-pantolactone of high optical purity, and they are also of little significance as practical processes for the preparation of D-pantolactone due to the fact that both the substrate concentration and the reaction rate are low.
As a result of extensive research on the asymmetric hydrolysis of D,L-pantolactone, the present inventors have previously found that D-pantolactone can be obtained efficiently from D,L-pantolactone through selective asymmetric hydrolysis by certain microorganisms of the D-pantolactone only in D,L-pantolactone to form D-pantoic acid, followed by separation, and conversion into D-pantolactone of the D-pantoic acid (see Japanese patent application No. 1-200347).
Thus, the present inventors have succeeded in providing a process for the preparation of D-pantolactone, characterized in that the D-pantolactone in D,L-pantolactone is selectively subjected to asymmetric hydrolysis using a microorganism possessing lactone-hydrolyzing ability selected from microorganisms belonging to the genera Fusarium, Cylndrocarpon, Gibbrella, Aspergillus, Penicillium, Rhizopus, Volutella, Gliocladium, Eurotium, Nectria, Schizophyllum, Myrothecium, Neurospora, Acremonium, Tuberculina, Absidia, Sporothrix, Verticillium or Arthroderma, to form D-pantoic acid, which is then separated and converted into D-pantolactone. The invention has many advantages over the above-mentioned known processes of selective asymmetric hydrolysis of the L-pantolactone in D,L-pantolactone, for example in that considerably higher substrate concentrations may be used, that shorter reaction times may be employed, and that D-pantolactone of extremely high optical purity can be obtained.